p-phenetidine is an important compound used as intermediate in the dyes industry as well as for many other uses. Thus for instance, it is used in the manufacture of p-ethoxyacetanilide and Ethoxyquin. Due to the large amounts of p-phenetidine required, there are many patents and publications which describe different methods, the aim in all of which being to improve the yield and purity of the product, thus reducing its cost.
The general scheme for the manufacture of p-phenetidine includes three main steps:
(a) Nitration of chlorobenzene by a mixture of sulfuric acid and nitric acid. The product obtained is a mixture of 70% p-chloro nitrobenzene and 30% o-chloro nitrobenzene. The o-nitro chlorobenzene obtained as a by-product, has to be recovered.
(b) Ethoxylation of the p-chloro nitrobenzene using a base and ethyl alcohol in the presence of a catalyst. The reaction is conducted for several hours, the chlorine being replaced by the ethoxy group. Yields in the range of 80% to 90% are mentioned to be obtained.
(c) Catalytic reduction of the nitro group at about 100.degree. C. under pressure in the presence of a catalyst selected from nickel or a noble metal. This reduction is carried out in the presence of a solvent which at the end of the reaction should be evaporated and the p-phenetidine is distilled out under vacuum.
Several improvements were suggested to the above scheme, all claiming that they improve the overall yield or costs of the final product. Some typical examples of a number of prior patents will be hereinafter described.
According to German Offen. 2,649,741, alkoxyanilines are prepared by treating the corresponding aniline with RX, wherein X is Cl or Br, in an aprotic organic solvent in the presence of an alkali metal alcoholate or hydroxide. The reaction is carried out in an autoclave at 80.degree. C. for 5 hours obtaining the alkoxyaniline at an yield of 89.5%.
According to Russian Patent Number 514,811, p-phenetidine is obtained by the reduction of p-nitrophenol in absolute alcohol in the presence of concentrated sulfuric acid, using platinum oxide as a catalyst and dimethyl sulfoxide as a promoter. The product is finally obtained by heating the mixture under a nitrogen medium.
According to Japanese Kokai 53/84925 (78/84925) alkoxy-anilines anilines are prepared by the reduction of p-nitrophenol with hydrogen dissolved in an alcohol in the presence of: organo-sulfonic acids or alkyl esters of sulfuric acid, platinum or paladium and sulfuric acid. The reaction is carried out under pressure for about seven hours at 70-80 degrees C., yielding 69% of p-alkoxyaniline.
According to Roumanian Patent Number 54273, p-phenetidine is obtained by the reduction of p-nitrophenetole with iron in an aqueous solution of ammonium chloride using a permanent excess of iron in the reaction medium exempt of free acidity. The precipitate of Fe.sub.3 O.sub.4 obtained was filtered under pressure and washed by steam. The filtrate was further treated with sodium chloride yielding the p-phenetidine.
An interesting process is described in the Czech Patent Number 146650 starting with phenol. In a first step the phenol is coupled with diazotized aniline and subsequently ethylated with ethyl chloride. The resulted product was cleaved at 30.degree.-60.degree. C. under pressure of hydrogen over a palladium on carbon catalyst. The yield claimed to be obtained is only about 90%.
The above brief review illustrates the importance attributed to the manufacture of p-phenetidine the aim being to improve some of the stages involved in the process, in order to increase the yield or purity of the final product.
It is an object of the present invention to provide a simple process for the manufacture of p-phenetidine. It is another object of the present invention to provide a simple process for the manufacture of p-phenetidine at high yields. It is yet another object of the present invention to provide a simple process for the manufacture of p-phenetidine which is substantially free of the undesired isomers o-phenetidine and chloro-amino aromatics.